A 2-pyrazoline derivative having an acyl group at position 1 can be prepared by reacting a 2-pyrazoline derivative with an acid chloride or acid anhydride.
The present inventors have described certain 1-acyl-2-pyrazoline derivatives having anti-cerebral edema activity as disclosed in our copending application Ser. No. 206,812 filed on June 15, 1988, now U.S. Pat. No 4,839,376 the disclosure of which is hereby incorporated by reference, and synthesized such derivatives according to the above-mentioned process.
This process, however, has a disadvantage in that the 2-pyrazoline derivative as the starting material is unstable and difficult to synthesize. For example, if 5-phenyl-2-pyrazoline is to be synthesized by the reaction of cinnamaldehyde with hydrazine, it is necessary to use a large excess of hydrazine relative to the amount of cinnamaldehyde to prevent the formation of azine. Azine is a condensation product formed by dehydration of two molecules of cinmamaldehyde and one molecule of hydrazine. And the separation of the desired 5-phenyl-2-pyrazoline is difficult because of residual cinnamaldehyde hydrazone, which is an uncyclized compound. In addition, it is known that 5-phenyl-2-pyrazoline is isomerized into 3-phenyl-2-pyrazoline during reaction or in the presence of a base, and that it changes into 5-phenylpyrazole upon oxidation by air. (S. G. Beech et al. J. Chem. Soc., 4686 (1952))
It is an object of the present invention to provide a new process for producing a 1-acyl-2-pyrazoline derivative, which is a useful compound as mentioned above, without forming unstable intermediates and undesirable by-products.
To achieve the above-mentioned object, the present inventors found a new process for producing a 1-acyl-2-pyrazoline derivative by the heat-induced cyclization of an acylhydrazone derivative. The present invention was completed on the basis of this finding.